Efficacy and Safety of Dalpiciclib Combined With Endocrine Adjuvant Therapy for Early HR +/HER2- Breast Cancer: a Multicenter, Prospective Clinical Study

Efficacy and Safety of Dalpiciclib Combined With Endocrine Adjuvant Therapy for Early HR +/HER2- Breast Cancer: a Multicenter, Prospective Clinical Study

This study is a multicenter, prospective, randomized, open-label clinical study to assess the efficacy and safety of endocrine combined with different doses and treatment duration of darisenatide adjuvant therapy in HR +/HER2- early breast cancer. The study planned to include 2000 HR +/HER2- early breast cancer patients who met the study criteria and were randomized in a 1:1 ratio to Column 1 and Column 2 stratified by nodal status (positive/negative), prior (neo) adjuvant chemotherapy (yes/no), and clinical/pathological stage (Stage II/III).

Cohort 1 received dalcili 125 mg in combination with endocrine therapy for 2 years with dalcili; Cohort 2 received dalcili 100 mg in combination with endocrine therapy for 3 years with dalcili; treatment had to be discontinued until disease progression, intolerable adverse events, withdrawal of consent, or investigator judgment.

Inclusion Criteria:

1. Female aged 18 years or older with breast cancer who are postmenopausal or premenopausal/perimenopausal.

2. Patients with early-stage breast cancer whose HR status is positive and HER2 status is negative, as confirmed by histology (immunohistochemistry showing ER ≥10% and/or PR ≥10%, HER2 0-1+ or HER2 ++ but negative by FISH or CISH testing, with no amplification).

3. Patients with histologically confirmed invasive breast cancer at clinical/pathological stages II-III.

   Note: For stage IIA, N1 is required, or N0 with Grade 3 or Grade 2 tumors combined with high-risk factors such as Ki-67 ≥20% or positive genetic testing (including but not limited to high-risk results in the 21-gene test). If the patient has previously received neoadjuvant therapy, the clinical stage at the time before neoadjuvant therapy must meet the above criteria.

4. Patients who have previously received or not received neoadjuvant chemotherapy or adjuvant chemotherapy are eligible to enroll.

5. The time interval from surgery to enrollment must not exceed 12 months.

6. Patients who have received radiotherapy must have recovered from the acute effects of radiotherapy, and there must be at least 14 days of washout period from the end of radiotherapy to enrollment.

7. Patients who have previously received chemotherapy must have recovered from the acute adverse effects of chemotherapy before enrollment ([CTCAE] grade ≤1), except for hair loss or grade 2 peripheral neuropathy.There must be a washout period of at least 21 days between the last administration of chemotherapy and enrollment in the study. 8. The Eastern Cooperative Oncology Group performance status score must be 0-1. 9. The functions of major organs must meet the following requirements: a) Blood tests: neutrophils (ANC) ≥1.5×10^9/L; platelet count (PLT) ≥90×10^9/L; hemoglobin (Hb) ≥90 g/L. b) Blood biochemistry tests: total bilirubin (TBIL) ≤2.5×ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5×ULN; alkaline phosphatase ≤2.5×ULN; blood urea nitrogen (BUN) and creatinine (Cr) ≤1.5×ULN. c) 12-lead electrocardiogram: QT interval corrected using the Fridericia method (QTcF) < 470 ms in females (QTcF calculation formula: QTcF = QT/(RR^1/3)). Participants must voluntarily agree to participate in the study, sign the informed consent form, demonstrate good compliance, and be willing to cooperate with follow-up assessments.

Exclusion Criteria:

1. Stage IV breast cancer or recurrent/metastatic breast cancer, or inflammatory breast cancer;
2. A history of any malignant tumor, or previous receipt of anti-tumor therapy or radiotherapy for any malignant tumor, excluding cured cases of cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma, etc.
3. Participating in other clinical trials simultaneously;
4. Received a blood transfusion within 2 weeks prior to enrollment, or received treatments such as colony-stimulating factors;
5. Individuals with a known history of allergy to any component of this medication;
6. A history of immunodeficiency, including a positive HIV test result, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation.
7. Any history of heart disease, including: (1) angina pectoris; (2) arrhythmias that require medical treatment or are clinically significant; (3) myocardial infarction; (4) heart failure; (5) any other heart disease deemed by the study investigators to be inappropriate for participation in this trial.
8. Pregnant or lactating female patients; 9. Any other circumstances in which the researchers deem the participant unsuitable for participating in this study.